Affinage

TRAF2

TRAF family member-associated NF-kappa-B activator · UniProt Q92844

Length
425 aa
Mass
47.8 kDa
Annotated
2026-06-10
100 papers in source corpus 49 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TRAF2 is a trimeric RING-domain E3 ubiquitin ligase and scaffolding adaptor that couples TNF receptor superfamily members to NF-κB and stress-kinase signaling (PMID:7544915, PMID:10206649). Its TRAF-C domain self-associates into a trimer that recognizes an SXXE-type receptor motif, providing an avidity-based mechanism for recruitment to ligand-oligomerized receptors such as TNF-R2 and CD40 (PMID:10206649), and TRAF2 is required for canonical NF-κB activation downstream of these receptors and of the LIGHT-LTβR axis (PMID:7544915, PMID:15539150, PMID:15743811). Genetically, TRAF2 is a positive regulator of canonical NF-κB but a negative regulator of the noncanonical pathway: it scaffolds K63-ubiquitination of cIAP1/cIAP2 to drive TRAF3 degradation and thereby keeps NIK destabilized, so its loss abolishes CD40-induced canonical signaling while constitutively activating p100-to-p52 processing (PMID:18997792, PMID:15539150). TRAF2 separately drives JNK activation through a TRAF2–ASK1/MLK3 kinase cascade that requires Ubc13-dependent K63-ubiquitination of TRAF2 and its translocation to a detergent-insoluble compartment (PMID:9774977, PMID:14713952, PMID:19918265). Beyond receptor signaling, TRAF2's catalytic activity targets diverse substrates: it K63-ubiquitinates GβL (MLST8) to bias mTORC1 over mTORC2 formation (PMID:28489822) and ubiquitinates RIPK1 to suppress necroptotic and apoptotic cell death while restraining the MLKL necrosome (PMID:25882049, PMID:35983756). TRAF2 abundance is itself a tightly regulated signaling node, set by K48-linked ubiquitination and proteasomal degradation by cIAP1 (with the ER E2 Ubc6) and opposed by the deubiquitinases CYLD, USP48, UCHL3, and OTUD7b, as well as by phosphorylation (PKC, IKKε at Ser11) and SMYD2 methylation (PMID:11907583, PMID:19150425, PMID:15861135, PMID:23007157, PMID:37516734, PMID:31477831). In vivo, conditional deletion links TRAF2 to epithelial inflammation, hepatocellular carcinoma, and cardiac homeostasis (PMID:26701909, PMID:28017612, PMID:35983756).

Mechanistic history

Synthesis pass · year-by-year structured walk · 24 steps
  1. 1995 High

    Established TRAF2 as a shared signaling mediator by showing it is necessary and sufficient for receptor-driven NF-κB activation.

    Evidence Overexpression and RING-deleted dominant-negative analysis with NF-κB reporters across TNF-R2 and CD40

    PMID:7544915

    Open questions at the time
    • Endogenous requirement not yet shown genetically
    • RING-domain enzymatic activity not yet defined
  2. 1998 High

    Defined the TRAF2–ASK1 link that routes TNF signaling into the JNK arm distinct from NF-κB.

    Evidence TNF-dependent reciprocal Co-IP plus catalytically inactive ASK1 dominant-negative and JNK assays

    PMID:9774977

    Open questions at the time
    • How TRAF2 activates ASK1 mechanistically not resolved
    • Role of TRAF2 ubiquitination not yet implicated
  3. 1999 High

    Provided the structural basis for receptor-oligomerization-dependent recruitment by showing TRAF2 trimerizes and binds an SXXE consensus motif.

    Evidence X-ray crystallography of the TRAF domain alone and bound to TNF-R2 peptide with solution validation

    PMID:10206649

    Open questions at the time
    • Structure of full-length protein with RING domain not solved
    • Conformational changes on activation not captured
  4. 1999 High

    Identified TRAF2-associated kinase complexes (TANK/TBK1) acting upstream of the IKK complex in NF-κB activation.

    Evidence Co-IP of ternary complex with kinase-dead TBK1 dominant-negative and NF-κB reporters

    PMID:10581243

    Open questions at the time
    • Physiological stimulus engaging this complex not defined
    • Endogenous requirement not tested genetically
  5. 2002 High

    Revealed that TRAF2 stability is actively controlled by cIAP1-mediated K48-ubiquitination, linking its turnover to apoptotic outcome.

    Evidence In vitro ubiquitination with E3-defective cIAP1 mutant, proteasome inhibitor and Co-IP in cells

    PMID:11907583

    Open questions at the time
    • Cognate E2 not identified at this stage
    • Subcellular site of degradation not localized
  6. 2004 High

    Separated TRAF2's roles using clean genetics, defining it as a positive regulator of canonical and a negative regulator of noncanonical NF-κB.

    Evidence B-cell-specific conditional knockout with NF-κB DNA-binding and proliferation assays

    PMID:15539150

    Open questions at the time
    • Molecular mechanism of noncanonical suppression not yet defined (resolved later)
  7. 2004 High

    Extended TRAF2 function to receptor-independent oxidative stress death via a RIP–TRAF2–JNK1 axis.

    Evidence TRAF2−/− and RIP−/− MEFs with reconstitution and H2O2-induced Co-IP and JNK assays

    PMID:15199146

    Open questions at the time
    • Sensor of ROS upstream of TRAF2-RIP complex unknown
  8. 2004 Medium

    Identified TRAF2-bound regulators (PKN1) and a cytoplasmic-retention role for cIAP1/2, expanding the adaptor interactome.

    Evidence Yeast two-hybrid, domain-mapped binding, RNAi/NF-κB assays and confocal localization

    PMID:14741690 PMID:15265700

    Open questions at the time
    • Single-lab interactions without independent confirmation
    • Physiological relevance of cIAP retention untested in vivo
  9. 2004 High

    Demonstrated that TRAF2 ubiquitination via its RING/zinc-finger and Ubc13 selectively drives JNK, not NF-κB or p38, coupled to insoluble-fraction translocation.

    Evidence Ubc13 RNAi, RING mutagenesis, subcellular fractionation with parallel pathway readouts

    PMID:14713952

    Open questions at the time
    • Identity of K63 chain attachment site not pinpointed here
    • Nature of insoluble compartment not defined
  10. 2005 High

    Localized cIAP1-mediated TRAF2 degradation to an ER-associated perinuclear compartment using the E2 Ubc6.

    Evidence Confocal ER co-localization, in vitro E2/E3 reconstitution and dominant-negative Ubc6

    PMID:15861135

    Open questions at the time
    • Trigger for ER translocation not defined
    • Single-study reconstitution
  11. 2005 High

    Distinguished LIGHT-LTβR signaling from TNFR1 by showing TRAF2 dependence but RIP- and TRAF5-independence.

    Evidence Multiple KO MEF lines with reconstitution and receptor complex immunoprecipitation

    PMID:12571250 PMID:15743811

    Open questions at the time
    • Apoptotic versus survival output balance not fully resolved
  12. 2008 High

    Resolved the mechanism of noncanonical suppression: TRAF2 K63-ubiquitinates cIAP1/2 to license TRAF3 degradation and NIK stabilization.

    Evidence Genetic deletion models with biochemical reconstitution and ubiquitination assays

    PMID:18997792

    Open questions at the time
    • Stoichiometry of the cIAP-TRAF2-TRAF3 complex addressed structurally only later
  13. 2009 High

    Defined the phosphorylation-to-ubiquitination relay: PKC-phosphorylated TRAF2 undergoes K63-ubiquitination at Lys31 to recruit IKK and TAB2/3.

    Evidence In vitro kinase assay, K31 mutagenesis, Co-IP and ubiquitination assays

    PMID:19150425

    Open questions at the time
    • Specific PKC isoform and kinase regulation not exhaustively mapped
  14. 2009 Medium

    Placed MLK3 as a TRAF2-specific JNK-pathway effector activated by K63-ubiquitination.

    Evidence TNF-dependent Co-IP, domain mapping, RNAi and MLK3 kinase activity assays

    PMID:19586614 PMID:19918265

    Open questions at the time
    • Single-lab findings
    • Whether MLK3 and ASK1 act redundantly or sequentially not resolved
  15. 2010 High

    Provided the structural stoichiometry of the TRAF2/cIAP2 and TRAF1:TRAF2:cIAP2 complexes, explaining how TRAF1 modulates cIAP recruitment.

    Evidence X-ray crystallography with interface mutagenesis and solution binding

    PMID:20385093

    Open questions at the time
    • Functional consequence of TRAF1 heterotrimer in vivo not fully tested
  16. 2012 High

    Identified IKKε phosphorylation of TRAF2 at Ser11 as an oncogenic driver promoting K63-ubiquitination and NF-κB.

    Evidence In vitro kinase assay, Ser11 mutagenesis, K63 ubiquitination and transformation assays

    PMID:23007157

    Open questions at the time
    • Crosstalk between Ser11 and Lys31 modifications not dissected
  17. 2014 High

    Showed TRAF2 abundance is set by kinase-directed lysosomal degradation (HGK/MAP4K4) with consequences for T-cell cytokine programs.

    Evidence In vitro kinase assay and T-cell-specific conditional HGK knockout

    PMID:25098764

    Open questions at the time
    • Lysosomal versus proteasomal routing determinants unclear
  18. 2015 High

    Established TRAF2 as a constitutive necroptosis brake via MLKL binding and CYLD-controlled deubiquitination, and linked CYLD-TRAF2 to HSC quiescence through p38MAPK.

    Evidence Domain-mapped Co-IP, KO cells/mice, necrosome assays; CYLD-binding mutant and p38 inhibition in HSCs

    PMID:25824820 PMID:25882049

    Open questions at the time
    • How MLKL binding gates necrosome assembly mechanistically not fully defined
  19. 2015 High

    Demonstrated in vivo that TRAF2 RING-dependent E3 activity, not SphK1-derived S1P, drives TNF signaling in epithelium.

    Evidence Keratinocyte-specific Traf2 KO compared with Sphk1-deficient mice and signaling readouts

    PMID:26701909

    Open questions at the time
    • Reconciliation with earlier SphK-dependence claims not fully addressed
  20. 2017 High

    Expanded TRAF2 catalysis beyond immunity to metabolic control by K63-ubiquitinating GβL to bias mTORC1 over mTORC2, reversed by OTUD7b.

    Evidence In vitro ubiquitination, GβL site mutagenesis, Co-IP and genetic deletion in mice

    PMID:28489822

    Open questions at the time
    • How signaling stimuli toggle this ubiquitination not defined
  21. 2017 Medium

    Identified additional deubiquitinases and phosphatases (USP48, PKCζ/Ser55, PP4R1) that fine-tune TRAF2 stability and output.

    Evidence Co-IP, K48-ubiquitination and phosphatase assays, site mutagenesis with pathway readouts

    PMID:25134449 PMID:28726782 PMID:28874458

    Open questions at the time
    • Single-lab studies
    • Context specificity of each regulator not cross-validated
  22. 2019 High

    Showed UCHL3 and OTUD7b stabilize TRAF2 by removing K48 chains, enabling RIPK1 K63-ubiquitination and survival signaling in cancer and DCs.

    Evidence Co-IP, K48/K63-specific ubiquitination assays, conditional KO and tumor/infection models

    PMID:31477831 PMID:37516734

    Open questions at the time
    • Which DUB dominates in a given cell type unresolved
  23. 2022 High

    Connected TRAF2 degradation to cardiac injury: doxorubicin-driven cIAP1-mediated TRAF2 loss impairs RIPK1 ubiquitination and NF-κB, with RING-dependent rescue in vivo.

    Evidence DOX mouse model, iPSC-cardiomyocytes, RING mutant and AAV9 cardiac overexpression

    PMID:35983756

    Open questions at the time
    • Mitochondrial protective mechanism downstream of NF-κB not fully delineated
  24. 2023 Medium

    Identified new K63 substrates (p62, DYRK1A) linking TRAF2 to mTORC1 activation and EGFR trafficking in cancer.

    Evidence Proteomics/Co-IP with site-directed ubiquitination mutagenesis and in vivo tumor models

    PMID:34117217 PMID:37081115

    Open questions at the time
    • Single-lab substrate assignments
    • Selectivity among TRAF2 substrates not explained

Open questions

Synthesis pass · forward-looking unresolved questions
  • How TRAF2 selects among its many K63 substrates and how the competing K48-degradative versus K63-signaling fates are coordinated in a single cell remains unresolved.
  • No unified model integrating phosphorylation, methylation and DUB inputs onto substrate choice
  • Quantitative dynamics of TRAF2 pools across compartments unmeasured

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016874 ligase activity 6 GO:0140096 catalytic activity, acting on a protein 5 GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 2 GO:0005783 endoplasmic reticulum 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-392499 Metabolism of proteins 5 R-HSA-168256 Immune System 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-1430728 Metabolism 2
Partners
ASK1CIAP1CIAP2CYLDMLK3MLKLRIPK1TRAF3
Complex memberships
LTβR signaling complexTRAF1:TRAF2:cIAP2TRAF2:TANK:TBK1TRAF2:cIAP1/cIAP2

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 TRAF2 overexpression is sufficient to activate NF-κB, and a truncated TRAF2 lacking the N-terminal RING finger domain acts as a dominant-negative inhibitor of NF-κB activation by TNF-R2 and CD40, establishing TRAF2 as a common mediator of TNF-R2 and CD40 signaling to NF-κB. Overexpression and dominant-negative mutant analysis in transfected cells; NF-κB reporter assays Science High 7544915
1998 ASK1 physically interacts with TRAF2 in a TNF-dependent manner and is activated by TRAF2 overexpression; a catalytically inactive ASK1 mutant blocks TRAF2-induced JNK activation, placing ASK1 downstream of TRAF2 in TNF-induced JNK signaling. Co-immunoprecipitation (endogenous, TNF-dependent), overexpression, dominant-negative kinase mutant, JNK activation assays Molecular Cell High 9774977
1999 TRAF2 forms a ternary signaling complex with TANK and TBK1 (a novel IKK-related kinase) that functions upstream of NIK and the IKK complex to activate NF-κB; complex formation is required for TBK1 kinase activity. Co-immunoprecipitation, kinase-dead TBK1 dominant-negative, NF-κB reporter assays EMBO Journal High 10581243
1999 Crystal structure of the TRAF2 TRAF domain reveals a trimeric self-association; the TRAF-C domain forms an eight-stranded antiparallel β-sandwich; TNF-R2 peptide binds a conserved shallow surface depression on one TRAF-C protomer; an SXXE motif is identified as a TRAF2-binding consensus sequence; trimeric structure provides avidity-based mechanism for receptor-oligomerization-dependent TRAF recruitment. X-ray crystallography (TRAF domain alone and in complex with TNF-R2 peptide), solution studies confirming trimeric assembly Nature High 10206649
1996 A20 interacts with TRAF1 and TRAF2 through its N-terminal domain binding to the conserved TRAF-C domain, and its C-terminal zinc finger domain mediates inhibition of TRAF2-induced NF-κB activation, defining a negative feedback loop. Co-immunoprecipitation, mutational analysis, co-transfection NF-κB reporter assays PNAS High 8692885
2002 TNF-RII engagement induces ubiquitination and proteasomal degradation of TRAF2 by c-IAP1, which binds TRAF2 in vitro and acts as an E3 ubiquitin ligase; an E3-defective c-IAP1 mutant prevents TRAF2 degradation and inhibits TNF-induced apoptosis. In vitro ubiquitination assay, E3-defective mutant, co-immunoprecipitation, proteasome inhibitor experiments Nature High 11907583
2004 TRAF2 ubiquitination via its RING and zinc finger domains, dependent on the E2 enzyme Ubc13, is required for TNFα-induced JNK activation but not for p38 or NF-κB activation; TRAF2 ubiquitination coincides with translocation to the insoluble cellular fraction. RNAi knockdown of Ubc13, RING domain mutagenesis, subcellular fractionation, JNK/IKK/p38 activation assays EMBO Journal High 14713952
2008 TRAF2 mediates K63-linked ubiquitination of cIAP1 and cIAP2, activating their E3 ubiquitin ligase activity toward TRAF3; upon CD40 or BAFF-R activation, cIAP1/2 ubiquitinate TRAF3 for degradation, releasing NIK from the cIAP1-cIAP2-TRAF2 complex, leading to NIK stabilization and NF-κB2-p100 processing (alternative NF-κB pathway). Genetic deletion models, ubiquitination assays, biochemical reconstitution of complex, immunoprecipitation Nature Immunology High 18997792
2009 PKC kinases phosphorylate TRAF2, facilitating recruitment of IKKα and IKKβ to the TNF receptor; phosphorylated TRAF2 undergoes K63-linked polyubiquitination at lysine 31, promoting TAB2/3 association and downstream IKK and JNK activation. In vitro phosphorylation assays, site-directed mutagenesis (K31), co-immunoprecipitation, ubiquitination assays Molecular Cell High 19150425
2010 Crystal structures of the TRAF2:cIAP2 and TRAF1:TRAF2:cIAP2 complexes show a TRAF2 trimer interacts with one cIAP2, with two chains of the TRAF2 trimer directly contacting cIAP2; TRAF1 preferentially forms a TRAF1:(TRAF2)₂ heterotrimer that binds cIAP2 more strongly, suggesting TRAF1 upregulation modulates TRAF2-cIAP1/2 interactions in TNF signaling. X-ray crystallography, mutagenesis of interface residues, solution binding studies Molecular Cell High 20385093
2017 TRAF2 acts as an E3 ubiquitin ligase that promotes K63-linked polyubiquitination of GβL (MLST8), disrupting its interaction with the mTORC2-specific component SIN1 to favor mTORC1 formation over mTORC2; the deubiquitinase OTUD7B reverses this to promote mTORC2 assembly. In vitro ubiquitination assay, Co-immunoprecipitation, mutagenesis of GβL ubiquitination sites (K305R/K313R), genetic deletion in mice Nature High 28489822
2004 In B cells lacking TRAF2, canonical NF-κB activation by CD40 ligation is abolished while noncanonical NF-κB (p100-to-p52 processing, RelB) is constitutively hyperactive, establishing TRAF2 as a positive regulator of canonical and negative regulator of noncanonical NF-κB. Conditional knockout mouse (B cell-specific TRAF2 deletion), NF-κB DNA binding assays, functional B cell proliferation assays Immunity High 15539150
2002 Sphingosine kinase (SphK) associates with TRAF2 via a TRAF2-binding motif, and this interaction activates SphK, which is required for TRAF2-mediated NF-κB activation and antiapoptotic signaling but not for JNK activation; dominant-negative SphK or SphK lacking the TRAF2-binding motif blocks NF-κB but not JNK. Co-immunoprecipitation, dominant-negative and binding-motif mutant SphK, NF-κB and JNK activation assays, apoptosis assays Journal of Biological Chemistry Medium 11777919
2005 Upon TNF-R2 signaling, TRAF2 and c-IAP1 translocate to a perinuclear, Triton X-100-insoluble compartment that co-localizes with the ER; the ER-resident E2 enzyme Ubc6 binds c-IAP1 and acts as a cognate E2 for c-IAP1-mediated TRAF2 ubiquitination in this compartment; catalytically inactive Ubc6 inhibits TNF-R2-dependent TRAF2 degradation. Confocal microscopy with ER markers, in vitro E2/E3 ubiquitination assay, dominant-negative Ubc6 mutant, subcellular fractionation EMBO Journal High 15861135
2006 GSTP1-1 physically associates with TRAF2 in vivo and in vitro via the TRAF domain-binding motif; GSTP1-1 overexpression inhibits TRAF2-induced JNK and p38 (but not NF-κB) activation by suppressing TRAF2-ASK1 interaction; GSTP1-1 RNAi increases TRAF2-ASK1 association and hyper-activates ASK1 and JNK. Co-immunoprecipitation (in vivo and in vitro), GSTP1-1 mutant lacking TRAF domain-binding motif, RNAi, kinase activation assays Oncogene Medium 16636664
2012 IKKε phosphorylates TRAF2 at Ser11 in vitro and in vivo; this phosphorylation promotes K63-linked TRAF2 ubiquitination and NF-κB activation, and is essential for IKKε-driven mammary epithelial cell transformation. In vitro kinase assay, site-directed mutagenesis (Ser11), K63 ubiquitination assay, transformation assays Molecular and Cellular Biology High 23007157
2015 TRAF2 constitutively associates with MLKL and suppresses necroptosis; TNFα reverses this via cylindromatosis (CYLD)-dependent TRAF2 deubiquitination; TRAF2 disruption augments RIPK3-MLKL necrosome formation; the C-terminal portion of TRAF2 (not the RING or CIM region) is required for MLKL interaction. Co-immunoprecipitation, TRAF2 domain deletion mutants, TRAF2 knockout cells and inducible KO mice, RIPK3/MLKL association assays, cell death assays Cell Death and Differentiation High 25882049
2015 CYLD deubiquitinates TRAF2 (its substrate); disruption of CYLD-TRAF2 interaction in HSCs promotes exit from quiescence and loss of self-renewal via p38MAPK pathway activation (not increased NF-κB), identifying CYLD-TRAF2-p38MAPK as a regulator of HSC dormancy. Conditional deletion of CYLD catalytic domain, CYLD mutant unable to bind TRAF2, pharmacological p38MAPK inhibition, HSC repopulation assays Journal of Experimental Medicine High 25824820
2004 TRAF2 is required for ROS (H₂O₂)-induced cell death in mouse embryonic fibroblasts; TRAF2⁻/⁻ MEFs are resistant to H₂O₂-induced death and cannot be rescued by TNFR1; RIP and TRAF2 form a complex upon H₂O₂ exposure independent of TNFR1; JNK1 activation downstream of RIP-TRAF2 mediates ROS-induced cell death. TRAF2⁻/⁻ MEFs, RIP⁻/⁻ MEFs, reconstitution of TRAF2 expression, co-immunoprecipitation, JNK activation assays Molecular and Cellular Biology High 15199146
2005 TRAF2 is critical for LIGHT-LTβR-mediated NF-κB and JNK activation; TRAF2⁻/⁻ MEFs lack both responses, which are restored by ectopic TRAF2; LIGHT induces recruitment of TRAF2, TRAF3, and IKK into the LTβR complex; unlike TNF signaling, LIGHT-LTβR activation is RIP- and TRAF5-independent. TRAF2⁻/⁻, RIP⁻/⁻, TRAF5⁻/⁻ MEFs, reconstitution, receptor complex immunoprecipitation, NF-κB and JNK assays Molecular and Cellular Biology High 15743811
2003 Endogenous TRAF2, TRAF3, cIAP1, and Smac associate with the LTβR signaling complex upon LIGHT stimulation, as identified by mass spectrometry and confirmed by co-immunoprecipitation in U937 and HEK293 cells; the presence of cIAP1 and Smac in this complex reveals a mechanism for LIGHT-LTβR-induced apoptosis. Affinity purification of endogenous complex followed by mass spectrometry; confirmatory co-immunoprecipitation Journal of Biological Chemistry Medium 12571250
2009 MLK3 interacts with TRAF2 (via TRAF domain of TRAF2 and C-terminal half of MLK3) in a TNFα-dependent manner; only TRAF2 (not TRAF5 or TRAF6) significantly induces MLK3 kinase activity; TRAF2 deletion mutant competing for MLK3 binding attenuates MLK3 activity; JNK activation by TNFα is TRAF2-dependent. Co-immunoprecipitation (endogenous, TNF-dependent), domain deletion mapping, dominant-negative competition, kinase activity assays Cell Research Medium 19918265
2009 TNF and IL-1β stimulation induces an interaction between MLK3 and TRAF2 (and TRAF6 for IL-1β); RNAi of traf2 dramatically impairs MLK3 activation by TNF; TNF stimulates K63-linked ubiquitination of MLK3 important for its kinase activity. RNAi knockdown of TRAF2, Co-immunoprecipitation, ubiquitination assays, MLK3 kinase activity assays Cellular Signalling Medium 19586614
2014 HGK (MAP4K4) directly phosphorylates TRAF2 leading to its lysosomal degradation; HGK deficiency in T cells stabilizes TRAF2 and elevates IL-6 production, promoting Th17 differentiation and insulin resistance. In vitro phosphorylation assay, conditional T-cell-specific HGK knockout, co-immunoprecipitation, lysosomal degradation assays Nature Communications High 25098764
2004 TRAF2 retains cIAP1 and cIAP2 in the cytoplasm by preventing their nuclear translocation; TNFα treatment reduces TRAF2-mediated cytoplasmic retention of cIAP1; co-expression of TRAF2 prevents nuclear accumulation of cIAP1 and cIAP2. Confocal microscopy, co-expression experiments, leptomycin B treatment, subcellular localization assays Experimental Cell Research Medium 15265700
2002 Cytoplasmic aggregation of TRAF2 and TRAF5 in Hodgkin-Reed-Sternberg cells co-localizes with IKKα, NIK, and IκBα, correlating with constitutive NF-κB activation; dominant-negative TRAF2 and TRAF5 suppress both aggregation and constitutive NF-κB. Confocal immunofluorescence microscopy, dominant-negative TRAF2 transfection, NF-κB activation assays American Journal of Pathology Medium 12000717
2015 TRAF2-mediated K63-linked ubiquitination of DUSP14 at K103 is required for DUSP14 phosphatase activity during TCR signaling; TRAF2 shRNA reduces DUSP14 ubiquitination. Mass spectrometry identification of ubiquitination site, K103 mutational analysis, TRAF2 shRNA, phosphatase activity assays Cellular Signalling Medium 26521044
2015 TRAF2 RING-dependent E3 ubiquitin ligase function is required for TNF-mediated NF-κB and MAP kinase signaling in keratinocytes; keratinocyte-specific TRAF2 deletion (but not SphK1 deficiency) disrupts TNF signaling and causes psoriatic skin inflammation, demonstrating that TRAF2's E3 activity does not require sphingosine-1-phosphate from SphK1. Keratinocyte-specific Traf2 conditional knockout mouse, comparison with Sphk1-deficient mice, NF-κB and MAP kinase signaling assays eLife High 26701909
2017 USP48 is a deubiquitinase that removes K48-linked polyubiquitin from TRAF2, stabilizing it specifically in the JNK pathway context; GSK3β phosphorylates USP48, increasing its DUB activity; USP48 knockdown reduces TRAF2 and attenuates TNFα/JNK signaling, increasing E-cadherin expression and epithelial barrier integrity. Co-immunoprecipitation, K48-ubiquitination assays, GSK3β phosphorylation assay, USP48 knockdown, E-cadherin/barrier assays FASEB Journal Medium 28874458
2019 OTUD7b deubiquitinase counteracts K48-linked ubiquitination and proteasomal degradation of TRAF2 in dendritic cells; stabilized TRAF2 facilitates K63-linked polyubiquitination of RIPK1, activating NF-κB and MAP kinases and inducing anti-apoptotic cFLIP/Bcl-xL expression; OTUD7b-deficient mice show DC apoptosis in infection. Co-immunoprecipitation, ubiquitination assays (K48/K63), DC-specific conditional OTUD7b knockout, murine infection model Cell Death & Disease High 37516734
2022 Doxorubicin causes cIAP1-mediated K48-ubiquitination and proteasomal degradation of TRAF2 in cardiac myocytes; loss of TRAF2 impairs K63-linked polyubiquitination of RIPK1 and NF-κB activation; TRAF2 RING-finger mutant (defective for K63-ubiquitination of RIPK1) fails to restore NF-κB signaling; cardiomyocyte-restricted TRAF2 overexpression in vivo protects against DOX-induced mitochondrial dysfunction and cardiac injury. In vivo DOX mouse model, iPSC-derived cardiomyocytes, ubiquitination assays, TRAF2 RING-finger mutant, AAV9-mediated cardiac-specific TRAF2 overexpression Circulation High 35983756
2016 Loss of RIPK1 in liver parenchymal cells causes TNF-dependent proteasomal degradation of TRAF2 in a RIPK1 kinase-independent manner, activating caspase-8; combined loss of RIPK1 and TRAF2 in liver causes caspase-8 hyperactivation, impaired NF-κB activation, and spontaneous hepatocellular carcinoma development. Liver-specific conditional RIPK1 and TRAF2 knockout mice, caspase-8 activity assays, NF-κB assays, tumor development analysis Cancer Cell High 28017612
2008 Smurf2 is a TRAF2-binding protein identified by yeast two-hybrid; TRAF2 overexpression triggers Smurf2 ubiquitination; Smurf2 promotes TNF-R2 ubiquitination and TNF-R2/TRAF2 relocalization to a detergent-insoluble fraction, enhancing TNF-R2-induced JNK activation without affecting NF-κB. Yeast two-hybrid screening, co-immunoprecipitation, ubiquitination assays, subcellular fractionation, JNK and NF-κB assays Biochemical and Biophysical Research Communications Medium 18671942
2015 TRAF2 functions as an activator switch for MST1 under oxidative stress: H₂O₂ induces physical interaction between TRAF2 and MST1, promoting MST1 homodimerization and activation; TRAF2 is required for H₂O₂-induced JNK, p38 activation, and apoptosis downstream of MST1. Co-immunoprecipitation (H₂O₂-dependent), MST1 homodimerization assays, TRAF2 knockdown, kinase activation assays Free Radical Biology & Medicine Medium 26698664
1998 CDK9 interacts with the conserved TRAF-C domain of TRAF2; endogenous interaction is specific to differentiated tissue; TRAF2-mediated signaling may incorporate CDK9 for cell survival in myotubes. Yeast two-hybrid screen, domain mapping, endogenous co-immunoprecipitation Journal of Cellular Biochemistry Low 9827693
2002 T2BP (TRAF2 binding protein) interacts with the TRAF domain of TRAF2 (confirmed by co-immunoprecipitation); overexpression of T2BP activates NF-κB and AP-1 in a dose-dependent manner without TNF stimulation. Mammalian two-hybrid screening, co-immunoprecipitation, NF-κB and AP-1 reporter assays Biochemical and Biophysical Research Communications Low 11798190
2006 The KSHV oncoprotein vFLIP contains a TRAF-interacting motif (PYQLT) and directly binds TRAF2 in vitro and in PEL cells; TRAF2 and TRAF3 are required for vFLIP-induced NF-κB activation and cell survival; TRAF2 (not TRAF3) mediates vFLIP association with the IKK complex; P93A/Q95A mutations in vFLIP abolish TRAF2 binding and NF-κB signaling. In vitro pulldown, co-immunoprecipitation in cells, dominant-negative TRAF2/3, vFLIP point mutants, NF-κB reporter assays EMBO Reports Medium 16311516
2004 PKN1 directly binds the TRAF domain of TRAF2 via a PXQX(S/T) motif (PIQES at residues 580-584); P580A/Q582A mutation abolishes co-immunoprecipitation; PKN1 RNAi downregulates TRAF2-induced NF-κB activation. Yeast two-hybrid, in vitro binding with TRAF2 deletion mutants, co-immunoprecipitation, PKN1 mutagenesis, RNAi, NF-κB reporter assays Biochemical and Biophysical Research Communications Medium 14741690
2014 TRAF2 interacts with the intracellular domain of LILRB3; activated LILRB3 recruits cFLIP via TRAF2, upregulating NF-κB to promote leukemic cell survival; hyperactivation of NF-κB induces A20-mediated negative feedback that disrupts LILRB3-TRAF2 interaction, switching to SHP-1/2-dominant inhibitory signaling. Co-immunoprecipitation, LILRB3 intracellular domain binding assays, NF-κB activation assays, antagonizing antibodies, functional leukemia models Nature Cancer Medium 35122056
2021 SMYD2 methyltransferase methylates TRAF2 (cytoplasmic protein), stabilizing it by restraining its own proteolysis and enhancing NF-κB signaling activity; the demethylase LSD1 reverses SMYD2-mediated TRAF2 methylation. Mass spectrometry identification of methylation site, pull-down, immunoprecipitation, methyltransferase assay, ubiquitination assay, luciferase reporter, SMYD2 loss/gain-of-function, in vivo inflammation models Clinical and Translational Medicine Medium 34841684
2023 TRAF2 acts as a K63-linked E3 ubiquitin ligase for p62, ubiquitinating it at K420; TRAF2-mediated p62 K63-ubiquitination activates mTORC1 by promoting the p62-mTORC1-Rag complex and lysosomal localization of mTORC1; TRAF2 depletion causes p62 accumulation and suppresses mTORC1 activity and liver cancer cell growth. Proteomics/Co-immunoprecipitation, K63-ubiquitination assay with K420 mutagenesis, mTORC1 lysosomal localization assays, in vivo tumor models Cell Death and Differentiation Medium 37081115
2019 UCHL3 deubiquitinase stabilizes TRAF2 by removing K48-linked ubiquitin chains, preventing proteasomal degradation; UCHL3-mediated TRAF2 stabilization activates NF-κB signaling in ovarian cancer. Co-immunoprecipitation, ubiquitination assays, UCHL3 knockdown, NF-κB luciferase assays, in vivo tumor models Oncogene Medium 31477831
2021 TRAF2 E3 ubiquitin ligase activity mediates K63-linked ubiquitination of DYRK1A at a PVQE motif-binding site, causing DYRK1A translocation to vesicle membranes; vesicle-localized DYRK1A phosphorylates Sprouty 2, inhibiting EGFR degradation; TRAF2 depletion accelerates EGFR degradation. Co-immunoprecipitation, K63-ubiquitination assay, subcellular localization by imaging, TRAF2 knockdown, EGFR degradation assays Cell Death & Disease Medium 34117217
2024 CD27 recruits TRAF2 and the phosphatase SHP-1 after ligand-induced internalization; the CD27-TRAF2-SHP-1 axis modulates TCR and CD28 signals during naive CD8+ T cell activation to promote memory-associated gene programs over effector differentiation. Co-immunoprecipitation of CD27-TRAF2-SHP-1 complex post-internalization, CD27 internalization imaging, gene expression profiling, CAR-T cell functional assays Immunity Medium 38354704
2017 TNFα stimulation induces TRAF2 to recruit GRK2 from the cytoplasm to the cell membrane; the TRAF2-GRK2 complex dissociates at the membrane, allowing GRK2 to desensitize and internalize EP4, reducing intracellular cAMP; TRAF2 siRNA abolishes TRAF2-GRK2 interaction and GRK2 membrane translocation. Co-immunoprecipitation (TRAF2-GRK2 complex), confocal microscopy for GRK2 translocation, cAMP FRET biosensor, TRAF2 siRNA knockdown Acta Pharmacologica Sinica Medium 33859345
2017 PKCζ phosphorylates TRAF2 at Ser55 (not Ser11) under intestinal ischemia-reperfusion or hypoxia/reoxygenation conditions; Ser55 phosphorylation promotes NF-κB activation and suppresses c-Jun activation, protecting against intestinal I/R-induced apoptosis. Co-immunoprecipitation (PKCζ-TRAF2), site-directed mutagenesis (Ser55, Ser11), NF-κB and AP-1 reporter assays, apoptosis assays, in vivo I/R model Cell Death & Disease Medium 28726782
2014 PP4R1 (regulatory subunit of protein phosphatase PP4) interacts with TRAF2 in a RING domain-dependent manner; PP4R1 dephosphorylates TRAF2 at Ser11; PP4R1 overexpression inhibits NF-κB activation by TRAF2, TRAF6, TNF, and LMP1; PP4R1 knockdown enhances LMP1 and TNF-induced IL-8 induction. Yeast two-hybrid, co-immunoprecipitation, RING domain mutagenesis, phosphatase activity assays (Ser11 dephosphorylation), NF-κB reporter assays, RNAi Cellular Signalling Medium 25134449
2011 EBV BRRF1 protein (Na) interacts with TRAF2 in cells (consistent with yeast two-hybrid); TRAF2 is required for Na-induced JNK activation and lytic gene expression in epithelial cells; a JNK inhibitor abolishes Na's ability to disrupt viral latency. Co-immunoprecipitation in cells, TRAF2 requirement assay (dominant-negative/knockdown), JNK inhibitor, lytic gene expression assays Journal of Virology Medium 21325409
2021 TRAF2 has an essential role in facilitating physiological mitophagy in cardiac myocytes via its E3 ubiquitin ligase activity; loss of cardiac TRAF2 leads to impaired mitophagy, triggering inflammation and cell death that impairs myocardial homeostasis. Conditional cardiac TRAF2 knockout, mitophagy assays, inflammatory marker measurements, cardiac phenotype analysis JACC Basic to Translational Science Medium 35411325

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40. Science (New York, N.Y.) 939 7544915
1998 ASK1 is essential for JNK/SAPK activation by TRAF2. Molecular cell 557 9774977
2008 Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling. Nature immunology 524 18997792
1999 NF-kappaB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. The EMBO journal 504 10581243
1997 TRAF2 is essential for JNK but not NF-kappaB activation and regulates lymphocyte proliferation and survival. Immunity 398 9390693
2002 TNF-RII and c-IAP1 mediate ubiquitination and degradation of TRAF2. Nature 389 11907583
1996 The tumor necrosis factor-inducible zinc finger protein A20 interacts with TRAF1/TRAF2 and inhibits NF-kappaB activation. Proceedings of the National Academy of Sciences of the United States of America 369 8692885
1999 Structural basis for self-association and receptor recognition of human TRAF2. Nature 306 10206649
2002 Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling. The Journal of biological chemistry 259 11777919
2016 TRAF2 multitasking in TNF receptor-induced signaling to NF-κB, MAP kinases and cell death. Biochemical pharmacology 198 26993379
2006 Human glutathione S-transferase P1-1 interacts with TRAF2 and regulates TRAF2-ASK1 signals. Oncogene 186 16636664
2004 Ubiquitination and translocation of TRAF2 is required for activation of JNK but not of p38 or NF-kappaB. The EMBO journal 179 14713952
2004 TRAF2 differentially regulates the canonical and noncanonical pathways of NF-kappaB activation in mature B cells. Immunity 179 15539150
2010 Crystal structures of the TRAF2: cIAP2 and the TRAF1: TRAF2: cIAP2 complexes: affinity, specificity, and regulation. Molecular cell 174 20385093
2017 TRAF2 and OTUD7B govern a ubiquitin-dependent switch that regulates mTORC2 signalling. Nature 164 28489822
2004 The Traf2- and Nck-interacting kinase as a putative effector of Rap2 to regulate actin cytoskeleton. The Journal of biological chemistry 143 15342639
2016 RIPK1 Suppresses a TRAF2-Dependent Pathway to Liver Cancer. Cancer cell 134 28017612
2012 Attenuation of TNFSF10/TRAIL-induced apoptosis by an autophagic survival pathway involving TRAF2- and RIPK1/RIP1-mediated MAPK8/JNK activation. Autophagy 132 23051914
2004 Essential roles of receptor-interacting protein and TRAF2 in oxidative stress-induced cell death. Molecular and cellular biology 118 15199146
2010 Traf2- and Nck-interacting kinase is essential for Wnt signaling and colorectal cancer growth. Cancer research 112 20530691
2009 PKC phosphorylation of TRAF2 mediates IKKalpha/beta recruitment and K63-linked polyubiquitination. Molecular cell 91 19150425
2015 TRAF2 regulates TNF and NF-κB signalling to suppress apoptosis and skin inflammation independently of Sphingosine kinase 1. eLife 90 26701909
2015 TRAF2 is a biologically important necroptosis suppressor. Cell death and differentiation 89 25882049
2005 TNF-alpha induced c-IAP1/TRAF2 complex translocation to a Ubc6-containing compartment and TRAF2 ubiquitination. The EMBO journal 88 15861135
2005 CD95 and TRAF2 promote invasiveness of pancreatic cancer cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 80 15670977
2020 Roflumilast prevents ischemic stroke-induced neuronal damage by restricting GSK3β-mediated oxidative stress and IRE1α/TRAF2/JNK pathway. Free radical biology & medicine 78 33359910
2014 HGK/MAP4K4 deficiency induces TRAF2 stabilization and Th17 differentiation leading to insulin resistance. Nature communications 77 25098764
2019 TRAF2 protects against cerebral ischemia-induced brain injury by suppressing necroptosis. Cell death & disease 72 30988281
2014 TRAF2 inhibits TRAIL- and CD95L-induced apoptosis and necroptosis. Cell death & disease 71 25299769
2022 Proteasomal Degradation of TRAF2 Mediates Mitochondrial Dysfunction in Doxorubicin-Cardiomyopathy. Circulation 68 35983756
2022 TNF Receptor Associated Factor 2 (TRAF2) Signaling in Cancer. Cancers 67 36011046
2007 Physiological roles and mechanisms of signaling by TRAF2 and TRAF5. Advances in experimental medicine and biology 66 17633015
2006 The KSHV oncoprotein vFLIP contains a TRAF-interacting motif and requires TRAF2 and TRAF3 for signalling. EMBO reports 65 16311516
2005 TRAF2: a double-edged sword? Science's STKE : signal transduction knowledge environment 64 15728425
2016 HOXA1 binds RBCK1/HOIL-1 and TRAF2 and modulates the TNF/NF-κB pathway in a transcription-independent manner. Nucleic acids research 62 27382069
2023 TRAF2 promotes M2-polarized tumor-associated macrophage infiltration, angiogenesis and cancer progression by inhibiting autophagy in clear cell renal cell carcinoma. Journal of experimental & clinical cancer research : CR 59 37415241
2016 MiR-502-5p inhibits IL-1β-induced chondrocyte injury by targeting TRAF2. Cellular immunology 56 26861148
2012 IκB kinase ε phosphorylates TRAF2 to promote mammary epithelial cell transformation. Molecular and cellular biology 56 23007157
2002 T2BP, a novel TRAF2 binding protein, can activate NF-kappaB and AP-1 without TNF stimulation. Biochemical and biophysical research communications 55 11798190
2021 LILRB3 supports acute myeloid leukemia development and regulates T-cell antitumor immune responses through the TRAF2-cFLIP-NF-κB signaling axis. Nature cancer 54 35122056
2019 UCHL3 promotes ovarian cancer progression by stabilizing TRAF2 to activate the NF-κB pathway. Oncogene 54 31477831
2002 Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in the Hodgkin-Reed-Sternberg cells. The American journal of pathology 52 12000717
2003 Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis. The Journal of biological chemistry 51 12571250
2015 Hematopoietic stem cell quiescence and function are controlled by the CYLD-TRAF2-p38MAPK pathway. The Journal of experimental medicine 47 25824820
2005 TRAF2 plays a key, nonredundant role in LIGHT-lymphotoxin beta receptor signaling. Molecular and cellular biology 44 15743811
2017 Wogonoside inhibits invasion and migration through suppressing TRAF2/4 expression in breast cancer. Journal of experimental & clinical cancer research : CR 41 28774312
2013 Downregulation of TRAF2 mediates NIK-induced pancreatic cancer cell proliferation and tumorigenicity. PloS one 40 23301098
2017 The deubiquitinating enzyme USP48 stabilizes TRAF2 and reduces E-cadherin-mediated adherens junctions. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 36 28874458
2015 Fbxo3-Dependent Fbxl2 Ubiquitination Mediates Neuropathic Allodynia through the TRAF2/TNIK/GluR1 Cascade. The Journal of neuroscience : the official journal of the Society for Neuroscience 35 26674878
2009 Cytokine-induced activation of mixed lineage kinase 3 requires TRAF2 and TRAF6. Cellular signalling 35 19586614
2004 Nuclear shuttling and TRAF2-mediated retention in the cytoplasm regulate the subcellular localization of cIAP1 and cIAP2. Experimental cell research 35 15265700
2022 SNHG15 is a negative regulator of inflammation by mediating TRAF2 ubiquitination in stroke-induced immunosuppression. Journal of neuroinflammation 34 34980176
2016 Comprehensive Modeling and Discovery of Mebendazole as a Novel TRAF2- and NCK-interacting Kinase Inhibitor. Scientific reports 34 27650168
2023 The TRAF2-p62 axis promotes proliferation and survival of liver cancer by activating mTORC1 pathway. Cell death and differentiation 32 37081115
2024 Signaling via a CD27-TRAF2-SHP-1 axis during naive T cell activation promotes memory-associated gene regulatory networks. Immunity 31 38354704
2015 Suppression of death receptor 5 enhances cancer cell invasion and metastasis through activation of caspase-8/TRAF2-mediated signaling. Oncotarget 31 26510914
2011 The Epstein-Barr virus BRRF1 protein, Na, induces lytic infection in a TRAF2- and p53-dependent manner. Journal of virology 31 21325409
1998 Binding of CDK9 to TRAF2. Journal of cellular biochemistry 31 9827693
2021 SMYD2-mediated TRAF2 methylation promotes the NF-κB signaling pathways in inflammatory diseases. Clinical and translational medicine 30 34841684
2018 TRAF2 in osteotropic breast cancer cells enhances skeletal tumour growth and promotes osteolysis. Scientific reports 30 29311633
2010 Traf2- and Nck-interacting kinase is essential for canonical Wnt signaling in Xenopus axis formation. The Journal of biological chemistry 29 20566648
2021 Ketamine enhances autophagy and endoplasmic reticulum stress in rats and SV-HUC-1 cells via activating IRE1-TRAF2-ASK1-JNK pathway. Cell cycle (Georgetown, Tex.) 28 34427546
2015 Blockade of CD40-TRAF2,3 or CD40-TRAF6 is sufficient to inhibit pro-inflammatory responses in non-haematopoietic cells. Immunology 28 25051892
2017 TRAF2 of black carp upregulates MAVS-mediated antiviral signaling during innate immune response. Fish & shellfish immunology 27 28964861
2015 TRAF2-mediated Lys63-linked ubiquitination of DUSP14/MKP6 is essential for its phosphatase activity. Cellular signalling 27 26521044
2015 TRAF2 functions as an activator switch in the reactive oxygen species-induced stimulation of MST1. Free radical biology & medicine 26 26698664
2009 TRAF2-MLK3 interaction is essential for TNF-alpha-induced MLK3 activation. Cell research 26 19918265
2003 TRAF2 exerts its antiapoptotic effect by regulating the expression of Krüppel-like factor LKLF. Molecular and cellular biology 26 12897154
2013 Cardiac-specific Traf2 overexpression enhances cardiac hypertrophy through activating AKT/GSK3β signaling. Gene 25 24378234
2021 TRAF2, an Innate Immune Sensor, Reciprocally Regulates Mitophagy and Inflammation to Maintain Cardiac Myocyte Homeostasis. JACC. Basic to translational science 24 35411325
2020 Pro-apoptotic functions of TRAF2 in p53-mediated apoptosis induced by cisplatin. The Journal of toxicological sciences 23 32238696
2014 The PP4R1 subunit of protein phosphatase PP4 targets TRAF2 and TRAF6 to mediate inhibition of NF-κB activation. Cellular signalling 22 25134449
2020 Pharmacological blockage of transforming growth factor-β signalling by a Traf2- and Nck-interacting kinase inhibitor, NCB-0846. British journal of cancer 21 33244122
2019 Cell type-specific function of TRAF2 and TRAF3 in regulating type I IFN induction. Cell & bioscience 21 30622699
2019 Decreased RIPK1 expression in chondrocytes alleviates osteoarthritis via the TRIF/MyD88-RIPK1-TRAF2 negative feedback loop. Aging 21 31606726
2016 Traf2- and Nck-interacting kinase (TNIK) is involved in the anti-cancer mechanism of dovitinib in human multiple myeloma IM-9 cells. Amino acids 21 26995282
2024 Oncogenic KEAP1 mutations activate TRAF2-NFκB signaling to prevent apoptosis in lung cancer cells. Redox biology 20 38184997
2017 TRADD, TRAF2, RIP1 and TAK1 are required for TNF-α-induced pro-labour mediators in human primary myometrial cells. American journal of reproductive immunology (New York, N.Y. : 1989) 20 28337828
2014 TRAF2 facilitates vaccinia virus replication by promoting rapid virus entry. Journal of virology 20 24429366
2023 The deubiquitinating enzyme OTUD7b protects dendritic cells from TNF-induced apoptosis by stabilizing the E3 ligase TRAF2. Cell death & disease 19 37516734
2008 Smurf2 is a TRAF2 binding protein that triggers TNF-R2 ubiquitination and TNF-R2-induced JNK activation. Biochemical and biophysical research communications 19 18671942
2025 Inflammation and cancer cell survival: TRAF2 as a key player. Cell death & disease 18 40229245
2022 Co-ordinated control of the ADP-heptose/ALPK1 signalling network by the E3 ligases TRAF6, TRAF2/c-IAP1 and LUBAC. The Biochemical journal 18 36098982
2021 K63-linked ubiquitination of DYRK1A by TRAF2 alleviates Sprouty 2-mediated degradation of EGFR. Cell death & disease 18 34117217
2020 Feasibility of Targeting Traf2-and-Nck-Interacting Kinase in Synovial Sarcoma. Cancers 18 32429395
2018 TRAF2 Cooperates with Focal Adhesion Signaling to Regulate Cancer Cell Susceptibility to Anoikis. Molecular cancer therapeutics 18 30373932
2004 Protein kinase PKN1 associates with TRAF2 and is involved in TRAF2-NF-kappaB signaling pathway. Biochemical and biophysical research communications 18 14741690
2021 TNF-α impairs EP4 signaling through the association of TRAF2-GRK2 in primary fibroblast-like synoviocytes. Acta pharmacologica Sinica 17 33859345
2019 TRAF2 Controls Death Receptor-Induced Caspase-8 Processing and Facilitates Proinflammatory Signaling. Frontiers in immunology 17 31555268
2018 WDR62 mediates TNFα-dependent JNK activation via TRAF2-MLK3 axis. Molecular biology of the cell 17 30091641
1998 TRAF2 expression in differentiated muscle. Journal of cellular biochemistry 17 9827692
2022 TSG-6 inhibits hypertrophic scar fibroblast proliferation by regulating IRE1α/TRAF2/NF-κB signalling. International wound journal 16 36056472
2017 PKCζ phosphorylates TRAF2 to protect against intestinal ischemia-reperfusion-induced injury. Cell death & disease 16 28726782
2007 Structural revelations of TRAF2 function in TNF receptor signaling pathway. Advances in experimental medicine and biology 16 17633020
2021 3,3'-diindolylmethane exerts antiproliferation and apoptosis induction by TRAF2-p38 axis in gastric cancer. Anti-cancer drugs 15 33315588
2021 Traf2 and NCK Interacting Kinase Is a Critical Regulator of Procollagen I Trafficking and Hepatic Fibrogenesis in Mice. Hepatology communications 15 34677004
2020 TRAF2 regulates T cell immunity by maintaining a Tpl2-ERK survival signaling axis in effector and memory CD8 T cells. Cellular & molecular immunology 15 33203937
2015 TRAF2 regulates peripheral CD8(+) T-cell and NKT-cell homeostasis by modulating sensitivity to IL-15. European journal of immunology 15 25931426
2015 TNFR-Associated Factor-2 (TRAF2): Not Only a Trimer. Biochemistry 15 26390021
2009 TRAF2 and TRAF3 independently mediate Ig class switching driven by CD40. International immunology 15 19228877

Missed literature

Know a paper Affinage missed for TRAF2? Flag it for the maintainers and the community.

No submissions yet.